A, Voltage clamp recording from Nav1.7 channels showing typical voltage-gated sodium currents. The downward deflection reflects the inward movement of sodium ions in response to a depolarizing voltage pulse from a holding potential of -80 mV. The channel is closed (C) at -80 mV and when pulsed to +15 mV the channel opens (O) and rapidly inactivates (I). B, A simple action potential schematic indicating where in the action potential waveform you would expect voltage-gated sodium channels to be closed, open, or inactivated. C, Diagram indicating the proposed scheme for voltage-gated sodium channels transitions from closed to open to fast-inactivated.